Near infrared readouts offer sensitive and rapid assessments of intestinal permeability and disease severity in inflammatory bowel disease models.

Autor: Zhang L; AbbVie Bioresearch Center, Worcester, MA, 01605, USA. liang.zhang@abbvie.com., Wallace CD; AbbVie Bioresearch Center, Worcester, MA, 01605, USA., Erickson JE; AbbVie Bioresearch Center, Worcester, MA, 01605, USA., Nelson CM; AbbVie Bioresearch Center, Worcester, MA, 01605, USA., Gaudette SM; AbbVie Bioresearch Center, Worcester, MA, 01605, USA., Pohl CS; AbbVie Inc, North Chicago, IL, 60064, USA., Karsen SD; AbbVie Bioresearch Center, Worcester, MA, 01605, USA., Simler GH; AbbVie Inc, North Chicago, IL, 60064, USA., Peng R; AbbVie Bioresearch Center, Worcester, MA, 01605, USA., Stedman CA; AbbVie Bioresearch Center, Worcester, MA, 01605, USA., Laroux FS; AbbVie Bioresearch Center, Worcester, MA, 01605, USA., Wurbel MA; AbbVie Bioresearch Center, Worcester, MA, 01605, USA., Kamath RV; AbbVie Bioresearch Center, Worcester, MA, 01605, USA., McRae BL; AbbVie Bioresearch Center, Worcester, MA, 01605, USA., Schwartz Sterman AJ; AbbVie Bioresearch Center, Worcester, MA, 01605, USA., Mitra S; AbbVie Bioresearch Center, Worcester, MA, 01605, USA.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Mar 13; Vol. 10 (1), pp. 4696. Date of Electronic Publication: 2020 Mar 13.
DOI: 10.1038/s41598-020-61756-y
Abstrakt: Intestinal permeability and neutrophil activity are closely linked to inflammatory bowel disease (IBD) pathophysiology. Here we discuss two techniques for assessing permeability and neutrophil activity in mouse IBD models using near infrared (NIR) detection. To address the limitation of visible light readouts-namely high background-IRDye 800CW was used to enable rapid, non-terminal measurements of intestinal permeability. The increased sensitivity of NIR readouts for colon permeability is shown using dextran sulfate sodium (DSS) and anti-CD40 murine colitis models in response to interleukin-22 immunoglobulin Fc (IL22Fc) fusion protein and anti-p40 monoclonal antibody treatments, respectively. In addition to enhanced permeability, elevated levels of neutrophil elastase (NE) have been reported in inflamed colonic mucosal tissue. Activatable NIR fluorescent probes have been extensively used for disease activity evaluation in oncologic animal models, and we demonstrate their translatability using a NE-activatable reagent to evaluate inflammation in DSS mice. Confocal laser endomicroscopy (CLE) and tissue imaging allow visualization of spatial NE activity throughout diseased colon as well as changes in disease severity from IL22Fc treatment. Our findings with the 800CW dye and the NE probe highlight the ease of their implementation in preclinical IBD research.
Databáze: MEDLINE
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